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RNA-induced silencing complex : ウィキペディア英語版
RNA-induced silencing complex
The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which incorporates one strand of a double-stranded RNA (dsRNA) fragment, such as small interfering RNA (siRNA) or microRNA (miRNA). The single strand acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, called Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in gene silencing and defence against viral infections.〔
〕〔

==Discovery==
The biochemical identification of RISC was conducted by Gregory Hannon and his colleagues at the Cold Spring Harbor Laboratory.〔
〕 This was only a couple of years after the discovery of RNA interference in 1998 by Andrew Fire and Craig Mello, who shared the 2006 Nobel Prize in Physiology or Medicine.〔
Hannon and his colleagues attempted to identify the RNAi mechanisms involved in gene silencing, by dsRNAs, in ''Drosophila'' cells. ''Drosophila'' S2 cells were transfected with a ''lacZ'' expression vector to quantify gene expression with β-galactosidase activity. Their results showed co-transfection with ''lacZ'' dsRNA significantly reduced β-galactosidase activity compared to control dsRNA. Therefore, dsRNAs control gene expression via sequence complementarity.
S2 cells were then transfected with ''Drosophila'' cyclin E dsRNA. Cycline E is an essential gene for cell cycle progression into the S phase. Cyclin E dsRNA arrested the cell cycle at the G1 phase (before the S phase). Therefore, RNAi can target endogenous genes.
In addition, cyclin E dsRNA only diminished cyclin E RNA — a similar result was also shown using dsRNA corresponding to cyclin A which acts in S, G2 and M phases of the cell cycle. This shows the characteristic hallmark of RNAi: the reduced levels of mRNAs correspond to the levels of dsRNA added.
To test whether their observation of decreased mRNA levels was a result of mRNA being targeted directly (as suggested by data from other systems), ''Drosophila'' S2 cells were transfected with either ''Drosophila'' cyclin E dsRNAs or ''lacZ'' dsRNAs and then incubated with synthetic mRNAs for cyclin E or ''lacZ''.
Cells transfected with cyclin E dsRNAs only showed degradation in cyclin E transcripts — the ''lacZ'' transcripts were stable. Conversely, cells transfected with ''lacZ'' dsRNAs only showed degradation in ''lacZ'' transcripts and not cyclin E transcripts. Their results led Hannon and his colleagues to suggest RNAi degrades target mRNA through a 'sequence-specific nuclease activity'. They termed the nuclease enzyme RISC.〔

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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